Tetranychus urticae (two-spotted spider mite, TSSM) is an extreme generalist herbivore with the ability to feed on over 1100 plant species. Its wide host range suggests that mites can disarm a wide array of host defenses. TSSM is a composite generalist herbivore. Its individual populations perform well only on a subset of plant species within their host range but can rapidly adapt to new plant hosts. The rapid xenobiotic adaptation is one of the key features underlying mites’ wide host range, allowing mites to render initially effective plant defenses, ineffective. Understanding the interaction between the mite and its host plant requires an understanding of plant defenses that were initially effective in limiting mite fitness, and an understanding of mite’s counteradaptations to host defenses. To study the mite-plant interaction, we experimentally adapted an ancestral bean-reared mite population to Arabidopsis. Arabidopsis is a challenging and non-preferred host for bean-reared mites, making it an excellent model to identify Arabidopsis defenses that restrict mite herbivory. While glucosinolates are considered a hallmark of Arabidopsis antiherbivore defenses, combined untargeted metabolomic and transcriptomic approaches are used to unbiasedly identify additional Arabidopsis compounds that restrict mite herbivory. On the mite side, a combination of untargeted metabolomics and transcriptomic approaches with RNAi and recombinant protein enzymatic studies are uncovering the complexity of mite detoxification mechanisms that are matching the complexity of Arabidopsis defenses. We identified novel Arabidopsis phytoalexins and phytoanticipins defining both constitutive and inducible defenses against spider mites. Inducible defenses accumulate both dependently and independently of canonical regulatory systems like MYC2,3,4 uncover the complexity of defense responses within a single plant species. Detoxification of some of the Arabidopsis defensive compounds has already been determined, demonstrating the complexity of mite xenobiotic responses.